MANIPULATION OF NAD+ IN C. ELEGANS AFFECTS HATCHING, LIFESPAN, AND SENSORY OUTPUT

Open Access
Author:
La Ganke, Nicole
Area of Honors:
Biochemistry and Molecular Biology
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Wendy Hanna-Rose, Thesis Supervisor
  • Teh-Hui Kao, Honors Advisor
Keywords:
  • Nicotinamide adenine dinucleotide
  • C. elegans
  • sirtuins
  • oxidative stress
  • lifespan
  • delayed hatching
  • sensory response
Abstract:
Nicotinamide adenine dinucleotide (NAD+) is a crucial molecule that is required for all living cells in mammals and C. elegans alike. The balance between the oxidized and reduced forms of NAD+ plays a role in energy transport and has been linked to regulation of multiple systems in the body. Three lines of research – reduction in NAD+, compromised activity of an NAD+ consumer, and manipulation of NAD+ biosynthetic precursors have all led to characteristic phenotypes that will be explored in this paper. I will show how manipulation of the concentration of NAD+ has led to the discovery of a novel phenotype in C. elegans called the delayed hatching phenotype. This phenotype is dependent on the interaction between a genotype and an environmental stimulus to produce delayed hatching. I have found when NAD+ levels are reduced through the riboside pathway and animals are grown in an increased level of oxidative stress, the embryos hatch up to 10 days after being laid in comparison to the wild-type animals hatching in 16 hours. NAD+ is also a cofactor to many proteins such as sirtuins. Sirtuins are a class of enzymes that regulate biochemical pathways and play a role in stress response and aging. In this study, I will show how knocking down two different mitochondrial sirtuins increases the lifespan of C. elegans in the presence of different food sources of varying pathogenicity. In addition, I will show how increasing oxidative stress levels affects the observed lifespan extension. Lastly, manipulation of the biosynthetic precursor of NAD+ such as nicotinamide, a form of vitamin B3, has an effect on sensory output. When the salvage synthesis pathway of NAD+ production is manipulated, a negative nose touch response rate is observed.